BACKGROUND The optimal target in the dorsolateral prefrontal cortex for treating depression with repetitive transcranial magnetic stimulation (rTMS) remains unknown. Better efficacy has been associated with stimulation sites that are 1) more anterior and lateral and 2) more functionally connected to the subgenual cingulate. Here we prospectively test whether these factors predict response in individual patients. METHODS A primary cohort (Boston, n = 25) with medication-refractory depression underwent conventional open-label rTMS to the left dorsolateral prefrontal cortex. A secondary cohort (Michigan, n = 16) underwent 4 weeks of sham followed by open-label rTMS for nonresponders (n = 12). In each patient, the location of the stimulation site was recorded with frameless stereotaxy. Connectivity between each patient's stimulation site and the subgenual cingulate was assessed using resting-state functional connectivity magnetic resonance imaging from a cohort of healthy subjects (n = 1000) and confirmed using connectivity from patients with depression (n = 38). RESULTS In our primary cohort, antidepressant efficacy was predicted by stimulation sites that were both more anterolateral (r = .51, p < .01) and more negatively correlated with the subgenual cingulate (r = -.55, p < .005). However, subgenual connectivity was the only independent predictor of response and the only factor to predict response to active (r = -.52, p < .05) but not sham rTMS in our secondary cohort. CONCLUSIONS This study provides prospective validation that functional connectivity between an individual's rTMS cortical target and the subgenual cingulate predicts antidepressant response. Implications for improving the cortical rTMS target for depression are discussed.

中文翻译：

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亚膝关节连接预测经颅磁刺激部位的抗抑郁功效的前瞻性验证

背景 用重复经颅磁刺激 (rTMS) 治疗抑郁症的背外侧前额叶皮层的最佳靶点仍然未知。更好的功效与刺激部位有关，这些部位 1) 更前侧和侧侧，2) 在功能上与膝下扣带回相连。在这里，我们前瞻性地测试这些因素是否能预测个体患者的反应。方法 一个主要队列（波士顿，n = 25）患有药物难治性抑郁症，对左侧背外侧前额叶皮层进行了常规的开放标签 rTMS。二级队列（密歇根州，n = 16）接受了 4 周的假手术，然后对无反应者（n = 12）进行了开放标签 rTMS。在每个患者中，刺激部位的位置用无框立体定位记录。每个患者之间的连通性' s 刺激部位和膝下扣带回使用来自一组健康受试者（n = 1000）的静息状态功能连接磁共振成像进行评估，并使用来自抑郁症患者（n = 38）的连接进行确认。结果在我们的主要队列中，抗抑郁药的疗效是由更前外侧（r = .51，p < .01）和与膝下扣带回更负相关（r = -.55，p < .005）的刺激位点预测的。然而，亚膝关节连接是反应的唯一独立预测因子，也是预测对活动反应的唯一因素（r = -.52，p < .05），但不是我们次要队列中的假 rTMS。结论 本研究提供了前瞻性验证，即个体之间的功能连接 s rTMS 皮质靶标和膝下扣带回预测抗抑郁反应。讨论了改善抑郁症皮质 rTMS 目标的意义。